1. Field of the Invention
The present invention is related to an innovative method to select acute tubular necrosis-related acute renal failure patient by detecting protein or nucleotide of annexin A2 and/or S100A6.
2. Description of the Prior Art
Acute tubular necrosis (ATN) is the most common pathologic entity responsible for the clinical state of acute renal failure (ARF) [1, 2]. The two main causes of ATN are ischemic and toxic injuries [3]. In the latter type, a variety of renal environmental substances that include heavy metals such as mercury, lead, and uranium are known to cause ARF. Nephrotoxic ATN is histologically evident as epithelial cell necrosis, mainly in the proximal convoluted tubules, with preservation of the tubular basement membrane, and usually intact distal tubular segments [4].
Although severely damaged by toxin, the kidney has the ability to completely recover structurally and functionally. Normally, quiescent cells undergo dedifferentiation and regain their potential to divide after enhancement of DNA synthesis in ATN. Consequent to cell proliferation, the new cells differentiate to restore the functional integrity of the nephron [5]. Little is known of the mechanism (s) by which regeneration of renal tubules is mediated. The observations that hepatocyte growth factor, epidermal growth factor, and bone morphogenetic protein-7 are among the potent regulators of kidney organogenesis, and that these agents can also promote tubular regeneration after a variety of insults [6], are consistent with the idea that the regeneration process may be partially controlled by a mechanism similar to that operating during development. Tubular cell calcium concentration and content are increased following acute renal injury induced by ischemic and toxic insults. The divalent calcium cation (Ca2+)-signaling system operate by binding to effector molecules, Ca2+-binding proteins, that mediate stimulation of numerous Ca2+-dependent processes such as transcription and cell proliferation. Two large families of the Ca2+-binding proteins are the annexins and the EF-hand motif S100 proteins [7]. The annexins are a family of 5 phospholipids binding proteins that share a common property of interacting with membranes and target molecules in a Ca2+-dependent manner [8, 9]. S100 proteins represent the largest subgroup in the EF-hand Ca2+-binding protein family. A unique feature of S100 proteins is that individual members are localized in specific cellular compartments from which some are able to relocate upon Ca2+ activation, thus transducing the Ca2+ signal in a temporal and spatial manner by interacting with different targets specific for each S100 protein [10]. Interactions between annexins and S100 proteins are now known to include several members of these protein families.
Therefore, it's helpful to search useful biomarkers in annexins and S100 protein groups for detecting the reason of acute kidney failure in clinical medical diagnosis.